title: Inflammatory demyelination induces glia alterations and ganglion cell loss in the retina of an experimental autoimmune encephalomyelitis model.
abstract: BACKGROUND
  Multiple sclerosis (MS) is often accompanied by optic nerve inflammation. And some patients experience permanent vision loss. We examined if the grade of optic nerve infiltration and demyelination affects the severity of clinical signs in an experimental autoimmune encephalomyelitis (EAE) model. The loss of retinal ganglion cells (RGC) and alterations in glia activity were also investigated.
  
  
  METHODS
  C57BL/6 mice were immunized with peptide MOG35-55 in complete Freund's adjuvant (CFA) and controls received PBS in CFA. Then 23 days post immunization eyes were prepared for flatmounts and stained with Nissl to evaluated neuronal density. Clinical EAE symptoms as well as cell infiltration and demyelination in the optic nerve were examined. Retinal sections were stained with hematoxylin and eosin and silver stain. Immunohistochemistry was used to label RGCs (Brn-3a), apoptotic cells (caspase 3), macroglia (glial fibrillary acidic protein (GFAP)), microglia (Iba1), macrophages (F 4/80) and interleukin-6 (IL-6) secretion.
  
  
  RESULTS
  EAE symptoms started at day 8 and peaked at day 15. Cell infiltrations (P = 0.0047) and demyelination (P = 0.0018) of EAE nerves correlated with the clinical score (r > 0.8). EAE led to a significant loss of RGCs (P< 0.0001). Significantly more caspase 3+ cells were noted in these animals (P = 0.0222). They showed an increased expression of GFAP (P< 0.0002) and a higher number of microglial cells (P< 0.0001). Also more macrophages and IL-6 secretion were observed in EAE mice.
  
  
  CONCLUSIONS
  MOG immunization leads to optic neuritis and RGC loss. EAE severity is related to the severity of optic nerve inflammation and demyelination. EAE not only affects activation of apoptotic signals, but also causes a glial response in the retina.
authors.affiliation: Experimental Eye Research Institute, Ruhr University Eye Hospital, In der Schornau 23-25, 44892 Bochum, Germany. stephanie.joachim@rub.de.
authors.forename: Lioba
authors.initials: L
authors.lastname: Horstmann
authors.forename: Heiko
authors.initials: H
authors.lastname: Schmid
authors.forename: André P
authors.initials: AP
authors.lastname: Heinen
authors.forename: Florian C
authors.initials: FC
authors.lastname: Kurschus
authors.forename: H Burkhard
authors.initials: HB
authors.lastname: Dick
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Joachim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D003711:Demyelinating Diseases / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D009902:Optic Neuritis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*